Neuronal and non-neuronal cells express the huntingtin (HTT) protein, yet neurodegeneration in Huntington's disease (HD) is largely selective, affecting most prominently striatal medium spiny neurons and cortical pyramidal neurons. Selective toxicity of full-length human mutant HTT (fl-mHTT) may be due in part to its expression in non-neuronal cells. While studies suggest neuronal-glial interactions are important in HD and fl-mHTT is expressed in astrocytes, it has not been determined whether the expression of fl-mHTT in astrocytes is necessary for HD pathogenesis. To directly assess the necessity of fl-mHTT in astrocytes for HD pathogenesis, we used a mouse genetic approach and bred the conditional mHTT-expressing BACHD mouse model with GFAP-CreER T2 mice. We show that GFAP-CreER T2 expression in these mice is highly selective for astrocytes, and we are able to significantly reduce the expression of fl-mHTT protein in the striatum and cortex of BACHD/GFAP-CreER T2-tam mice. We performed behavioral, electrophysiological and neuropathological analyses of BACHD and BACHD/GFAP-CreER T2-tam mice. Behavioral analyses of BACHD/GFAP-CreER T2-tam mice demonstrate significant improvements in motor and psychiatric-like phenotypes. We observe improvements in neuropathological and electrophysiological phenotypes in BACHD/GFAP-CreER T2-tam mice compared to BACHD mice. We observed a restoration of the normal level αB-crystallin in the striatum of the BACHD/GFAP-CreER T2 mice, indicating a cell autonomous effect of mHTT on its expression. Taken together, this work indicates that astrocytes are important contributors to the progression of the behavioral and neuropathological phenotypes observed in HD.

INTRODUCTIONIn 2010 a care bundle was introduced by the Department of Health (DH) to reduce surgical site infections (SSIs) in England. To date, use of the care bundle has not been evaluated despite incorporating interventions with resource implications. The aim of this study was to evaluate the DH SSI care bundle in open colorectal surgery. METHODS A prospective cohort design was used at two teaching hospitals in England. The baseline group consisted of 127 consecutive patients having colorectal surgery during a 6-month period while the intervention group comprised 166 patients in the subsequent 6 months. SSI and care bundle compliance data were collected using dedicated surveillance staff. RESULTS Just under a quarter (24%) of the patients in the baseline group developed a SSI compared with just over a quarter (28%) in the care bundle group (p>0.05). However, compliance rates with individual interventions, both before and after the implementation of the bundle, were similar. Interestingly, in only 19% of cases was there compliance with the total care bundle. The single intervention that showed an associated reduction in SSI was preoperative warming (p=0.032). CONCLUSIONS The DH care bundle did not reduce SSIs after open colorectal surgery. Despite this, it is not possible to state that the bundle is ineffective as compliance rates before and after bundle implementation were similar. All studies evaluating the effectiveness of care bundles must include data for compliance with interventions both before and after implementation of the care bundle; poor compliance may be one of the reasons for the lower than expected reduction of SSIs.

Inadequate transition to practice increases stress for new health care providers and threatens employment longevity. This integrative review aimed to synthesize the evidence on transition process for newly graduated registered nurses and advanced practice nurses in hospital settings and to identify enablers/barriers and mitigating strategies. Two databases were systematically searched for articles that described the process, strategies, participant perceptions, and implications of role transition with a final yield of 23 articles. Synthesis of the evidence revealed three major themes: (a) achieving competence for safe practice, (b) addressing stress during transition, and (c) reducing turnover. Emotional support for new graduates was instrumental to achieving clinical competence. Role transition adaptation was linked to anxiety, while emotional health was positively associated with retention. Developing best practices that address skill proficiency, attending to the emotional needs of new nurse graduates, and providing structured transition programs to improve clinical competence are the strategies of choice.

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